Mouse neuroblastoma clones will be used as a model system to study the regulation of tyrosine hydroxylase and catecholamine synthesis. Electrical field stimulation, K ion stimulation as well as neurotransmitters and hormones suspected of playing a role in the regulation of tyrosine hydroxylase synthesis will be studied for their direct effect on tyrosine hydroxylase level in the cultured cells. cAMP, broken cell adenylate cyclase and phosphodiesterase will also be examined. Cyclic AMP, prostaglandin, and short chain organic acid stimulation of tyrosine hydroxylase synthesis will be characterized kinetically, and the requirements for macromolecular synthesis determined. The regulation of other norepinephrine biosynthetic enzymes, dopa decarboxylase, dopamine beta hydroxylase and dihydropteridine reductase will be correlated with induced changes in tyrosine hydroxylase. Their regulation may be linked to that of tyrosine hydroxylase. This model of the adrenergic neuron will be used to characterize tyrosine and phenylalanine uptake and the role that it and catecholamine feedback inhibition play in regulation of norepinephrine synthesis. Intact animal studies will be employed to examine the direct effect of increased nerve depolarization on the level of tyrosine hydroxylase and to evaluate the role that norepinephrine and prostaglandins play in the induction of this enzyme.